It has been well documented that injured articular cartilage has only a limited ability for self-repair. As articular cartilage is relatively avascular and aneural, loss of the surface tissue will result in a permanently scarred site. Lesions which fracture the subchondral bone which has a greater vascular supply will undergo an inflammation/repair response, with the damaged site filling with fibrocartilage tissue (Convery, et al. 1972). In either case, function is impaired and chronic pain is the usual prognosis as the biochemical and biomechanical characteristics of the cartilage have been altered. Current treatment protocols call for surgical intervention (such as abrasion arthroplasty, excision and drilling, articular cartilage debridement, and arthroscopic shaving) and will most often lead again to inadequate repair. Long-term morbidity such as degeneration to arthritic conditions will often result in patients with chronic cartilage problems.
Nevertheless, articular cartilage theoretically does have some intrinsic ability to heal after injury. For example, chondrocytes are capable of replication when isolated enzymatically from the cartilage matrix (Grande, et al., 1989). It has been suggested that cartilage repair can be initiated by either replication of chondrocytes in the regions adjacent to the defect, or by metaplasia of chondrocytes from other connective tissue stem cells within the joint capsule, such as from the synovium and subchondral bone (Sokoloff, 1978). Given this possibility, investigations of autograft or allograft tissue and tissue analogues to heal cartilage lesions has progressed.
Techniques were developed to utilize autologous tissue, such as transplantation of: 1) osteochondral graft (DePalma, et al., 1963); 2) chondrocytes (Grande, et al., 1989); 3) periosteum (Homminga, et al., 1990); and 4) demineralized bone (Dahlberg and Kreicbergs, 1991). These techniques have been used to transplant whole or partial joints, with mixed results. For example, a number of investigators attempted to heal cartilage defects using chondrocytes isolated from epiphyseal plates, as well as articular cells, with the hypothesis that these cells would have a greater chance of success due to their heightened metabolism (Itay, et al., 1987). Clinical studies using cultured cells reported excellent results, showing a significant decrease in pain and restoration of normal function after two to four years post-op (Iloika, et al., 1990; Ilomminga, et al., 1990).
Other investigations have used a combination of materials and autologous tissue to effectively repair cartilage defects, such as: 1) demineralized bone with perichondrium (Billings, et al., 1990); 2) polylactic acid matrices and periosteal grafts (von Schroeder, et al., 1991); and 3) bioresorbable meshes and chondrocytes (Freed, et al., 1993). Although these approaches gave repair tissue that more closely resembled normal cartilage than either the unfilled sites, or the sites filled with materials alone, it was evident that there was again a substantial amount of fibrocartilage formation.
In U.S. Pat. Nos. 4,505,266 and 4,458,678, Yannas et al. states in column 11 that various "types of fibrous lattices may be suitable for use as temporary prosthetic devices within most regions of the body, including skin, blood vessels, bones, connective tissue, contractile tissue and organs. Such lattices provide a structural system in which virtually any type of cell may grow, migrate and proliferate. They can be surgically emplaced within virtually any region of the body, and if properly seeded with the appropriate type(s) of cells, may allow for the regeneration of new tissue. For example, if a patient suffers damage to or disease of an organ, a portion of the organ may need to be removed. A fibrous lattice may be emplaced in the location created by removal of part of the organ. If a sufficient number of healthy cells from another part of that organ, or from a compatible donor, is seeded into the lattice by the methods of this invention, it may be possible to greatly promote the recovery and regeneration of the organ."
U.S. Pat. No. 4,846,835 discloses that chondrocytes that are grown in a three-dimensional collagen matrix can enhance the healing of articular cartilage lesions that do not fracture the subchondral plate.
In experiments in rabbits that followed the teachings of Yannas and Grande, cultured chondrocytes were seeded into a three-dimensional collagen matrix and the seeded matrix was implanted into a surgically-created articular cartilage lesion. Surprisingly, in view of those teachings, it was found that in addition to the presence of the desired hyaline-like cartilage, a substantial amount of undesirable fibro-cartilage was formed, apparently by fibroblasts that migrated into the matrix from the subchondral plate. Thus, these experiments indicate that neither Yannas nor Grande teach a method of forming a high quality hyaline-like cartilage suitable for repair of defects in articular cartilage because they do not provide a means to select against undesirable types of cells that can infiltrate the matrix from surrounding tissue. In the present invention, we have discovered a novel way to direct the growth of the desired hyaline-like cartilage, thus avoiding the difficulties of the prior art.